Aerosol generating devices and methods for generating aerosols having controlled particle sizes

ABSTRACT

An aerosol generating device includes a housing, a heater and an optional mouthpiece. The heater volatilizes liquid within a flow passage and forms an aerosol in the mouthpiece. An aerosol confinement sleeve is disposed to control the size distribution of the aerosol.

RELATED APPLICATIONS

[0001] This application claims priority under 35 U.S.C. § 119 to U.S.Provisional Application No. 60/408,291 entitled AEROSOL GENERATINGDEVICES AND METHODS FOR GENERATING AEROSOLS HAVING CONTROLLED PARTICLESIZES and filed on Sep. 6, 2002, the entire content of which is herebyincorporated by reference.

BACKGROUND

[0002] Aerosols are useful in a wide variety of applications. Forexample, aerosols have been used to treat respiratory ailments, or todeliver medicaments, by providing sprays of finely divided particles ofliquids and/or solids, such as powders, liquid medicaments, and thelike, which are inhaled by patients. Aerosols are also useful, forexample, for delivering desired scents to rooms, applying scents to theskin, and delivering paints and lubricants.

[0003] There are various known techniques for generating aerosols. Forexample, U.S. Pat. Nos. 4,811,731 and 4,627,432 disclose devices foradministrating medicaments to patients that include a capsule, which ispierced to release medicament in powder form. The user inhales thereleased medicament through an opening in the device. Medicaments inliquid form have been delivered by generating aerosols with a manuallyoperated pump. The pump draws liquid from a reservoir and forces itthrough a small opening to form a fine spray.

[0004] Alternatively, medicaments have been delivered by generating anaerosol including liquid or powder particles using a compressedpropellant, which entrains the medicament. Such inhalers are usuallyoperated by depressing an actuator to release a charge of the compressedpropellant, which contains the medicament, through a spray nozzle,allowing the propellant encapsulated medicament to be inhaled by theuser. However, it is difficult to properly synchronize the inhalation ofthe medicament with depression of the actuator. Further, desiredquantities of medicament or other materials are not suitably deliveredby this method.

[0005] Many aerosol generating devices also are unable to generateaerosols having an average mass median aerosol diameter (MMAD) less than2 to 4 microns, and to deliver high aerosol mass flow rates, such asabove 1 milligram per second, with particles in the size range of 0.2 to2.0 microns. A high aerosol mass flow rate and small particle size areparticularly desirable for enhanced penetration into the lungs duringmedicament administration, such as for asthma treatment.

[0006] Larger particles generated by inhalers may be deposited in themouth and pharynx of the patient, rather than inhaled into the lungs. Inaddition, larger inhaled particles may not penetrate into the lungs asdeeply as desired for certain applications.

[0007] Therefore, there is a need for an aerosol generating device thatcan provide different aerosol size distributions of aerosols, such thatthe device can be adapted to the different needs of a patient. Moreover,there is a need for an aerosol generating device that providescontrolled adjustability of the aerosol size distribution of aerosolsthat it produces.

SUMMARY

[0008] An aerosol generating device is provided that can produceaerosols having different aerosol size distributions. The aerosolgenerating device provides controlled adjustability of the aerosol sizedistribution, such that it can be used to provide aerosols that are mostsuitable to meet the needs of a user.

[0009] In a preferred embodiment, the aerosol generating devicecomprises a housing, a flow passage, a heater, a mouthpiece, a source ofliquid to be volatilized, and an aerosol confinement sleeve. Liquid issupplied into the flow passage from the source and heated in the flowpassage by the heater, thereby volatilizing the liquid. The aerosolconfinement sleeve is disposed about the outlet end of the flow passage.Volatilized material exiting the flow passage enters into the aerosolconfinement sleeve, which is configured to control the aerosol sizedistribution delivered by the aerosol generating device.

[0010] An embodiment of a method for generating an aerosol comprisessupplying a liquid to a flow passage; heating the liquid in the flowpassage to volatilize the liquid; and passing volatilized liquid out ofthe flow passage and into an aerosol confinement sleeve configured tocontrol an aerosol size distribution of an aerosol produced from thevolatilized liquid.

DRAWINGS

[0011]FIG. 1 illustrates an embodiment of an aerosol generating device.

[0012]FIG. 2 illustrates an embodiment of an arrangement including anaerosol confinement sleeve located at the outlet end of a flow passage.

[0013]FIG. 3 shows the relationship between the mass median aerodynamicdiameter (MMAD) of propylene glycol (PG) and the aerosol confinementsleeve length.

[0014]FIG. 4 shows the relationship between the percentage PG recoveryand the aerosol confinement sleeve length.

[0015]FIG. 5 shows the relationship between the MMAD of PG aerosolparticles and the air flow rate (inhalation rate) for two differentsized capillary passages.

[0016]FIG. 6 illustrates the relationship between aerosol particlediameter and PG flow rate in the flow passage for aerosols producedusing different sized flow passages.

[0017]FIG. 7 shows the size distributions of aerosol particles of PG andoleyl alcohol (OA) in an aerosol produced from a solution of OA in PG.

[0018]FIG. 8 shows the MMAD of aerosol particles of PG and OA inaerosols produced from solutions having different concentrations of OAin PG.

[0019]FIG. 9 shows the size distribution of aerosol particles ofbudesonide and PG in an aerosol produced from a solution of budesonidein PG.

[0020]FIG. 10 shows the size distribution of aerosol particles of PEG400 and PG in an aerosol produced from a solution of PEG 400 in PG.

[0021]FIG. 11 shows relationships between the MMAD of PG aerosolparticles and aerosol confinement sleeve length (Curve A), and betweenpercent PG recovery and aerosol confinement sleeve length (Curve B) fora mouthpiece having an inner diameter of 1.25 inch.

[0022]FIG. 12 shows relationships between the MMAD of PG aerosolparticles and aerosol confinement sleeve length (Curve A), and betweenpercent PG recovery and aerosol confinement sleeve length (Curve B) fora mouthpiece having an inner diameter of ⅞ inch.

[0023]FIG. 13 shows approximated air streamlines generated withmouthpieces having an inner diameter of 1.25 inch (A) and ⅞ inch (B).

[0024]FIG. 14 shows the relationship between the MMAD of PG aerosolparticles and aerosol confinement sleeve length for mouthpieces havingan inner diameter of 1.25 inch and ⅞ inch.

[0025]FIG. 15 shows relationships between the MMAD of PG aerosolparticles and air flow rate (Curve A), and between percent PG recoveryand air flow rate (Curve B) for a mouthpiece having an inner diameter of¾ inch.

[0026]FIG. 16 shows relationships between the MMAD of PG aerosolparticles and aerosol confinement sleeve length (Curve A), and betweenpercent PG recovery and aerosol confinement sleeve length (Curve B) foran aerosol confinement sleeve having an inner diameter of ⅜ inch for aPG flow rate of 10 mg/sec.

[0027]FIG. 17 shows relationships between the MMAD of PG aerosolparticles and aerosol confinement sleeve length (Curve A), and betweenpercent PG recovery and aerosol confinement sleeve length (Curve B), foran aerosol confinement sleeve having an inner diameter of ⅜ inch and aPG flow rate of 5 mg/sec.

[0028]FIG. 18 shows relationships between the MMAD of PG aerosolparticles and aerosol confinement sleeve length (Curve A), and betweenpercent PG recovery and aerosol confinement sleeve length (Curve B) foran aerosol confinement sleeve having an inner diameter of ¼ inch and ata PG flow rate of 10 mg/sec.

[0029]FIG. 19 shows size distributions for PG aerosol particles (CurveC) and albuterol aerosol particles (Curve D) produced with a 1% w/walbuterol in PG solution with an aerosol confinement sleeve, and for PGaerosol particles (Curve A) and albuterol aerosol particles (Curve B)produced without the aerosol confinement sleeve.

[0030]FIG. 20 shows PG total aerosol particle size distributionsproduced with a 0.5% w/w albuterol in PG solution without an aerosolconfinement sleeve (Curve A), and produced with an aerosol confinementsleeve having a length of 1 inch (Curve B), 1.25 inch (Curve C), and 1.5inch (Curve D).

[0031]FIG. 21 shows albuterol aerosol particle size distributionsproduced with a 0.5% w/w albuterol in PG solution without an aerosolconfinement sleeve (Curve A), and produced with an aerosol confinementsleeve having a length of 1 inch (Curve B), 1.25 inch (Curve C), and 1.5inch (Curve D).

[0032]FIG. 22 shows relationships between triacetin aerosol particlesize and aerosol confinement sleeve length (Curve A), and betweentriacetin recovery and aerosol confinement sleeve length (Curve B) foran aerosol confinement sleeve having an inner diameter of 0.5 inch.

[0033]FIG. 23 shows relationships between the MMAD of OA aerosolparticles and aerosol confinement sleeve length (Curve A), and betweenpercent PG recovery and aerosol confinement sleeve length (Curve B) fora 5% w/w OA in PG solution and using an aerosol confinement sleevehaving a ½ inch inner diameter.

[0034]FIG. 24 shows relationships between the MMAD of PG aerosolparticles and aerosol confinement sleeve length (Curve A), and betweenPG recovery and aerosol confinement sleeve length (Curve B) for a 5% w/wOA in PG solution with an aerosol confinement sleeve having a ½ inchinner diameter.

[0035]FIG. 25 shows the aerosol particle distribution for OA producedwithout an aerosol confinement sleeve (Curve A), and produced with anaerosol confinement sleeve having a length of 0.75 inch (Curve B), 1inch (Curve C), 1.25 inch (Curve D), and 1.5 inch (Curve E).

[0036]FIG. 26 shows the relationship between the MMAD of OA aerosolparticles and air flow rate for a 5% w/w OA in PG solution.

[0037]FIG. 27 shows the relationship between the MMAD of PG aerosolparticles and air flow rate for a 5% w/w OA in PG solution.

DETAILED DESCRIPTION

[0038] An aerosol generating device is provided, which can be operatedto produce aerosols having a controlled particle size distribution. Theaerosol generating device includes an aerosol confinement sleeve, whichcontrols the particle size distribution of aerosols. In a preferredembodiment, the aerosol generating device includes a replaceable aerosolconfinement sleeve, which permits a user or manufacturer to change theaerosol confinement sleeve to provide a different aerosol particle sizedistribution.

[0039]FIG. 1 depicts a preferred embodiment of a hand-held aerosolgenerating device 120. The aerosol generating device 120 comprises ahousing 121, a source 122 of a liquid aerosol formulation, a controller124, a power source 126, an optional sensor 127, such as a pressuresensor, a heated flow passage 128, a valve 130, and a mouthpiece 132.The valve 130 is operable to deliver a volume of fluid, such as apredetermined dose, from the source 122 to the flow passage 128.

[0040] The controller 124 is operably connected to the power source 126,the sensor 127 and valve 130 to effect delivery of the liquid from thesource 122 to the flow passage 128, and to operate a heater arranged toheat liquid in the flow passage 128. For example, in a preferredembodiment, the flow passage comprises a capillary sized flow passage.For example, the capillary sized flow passage can be tube oralternatively a passage in a body, such as a monolithic or multilayerbody of an electrically insulating material.

[0041] In a preferred embodiment, the heated flow passage 128 comprisesan electrically conductive material, such as a metallic tube (e.g.,stainless steel), or a non-conductive or semi-conductive tubeincorporating a heater made of an electrically conductive material, suchas platinum, or the like. The flow passage is preferably a capillarysized passage of uniform cross-section along its length. In suchembodiments, the flow passage can have any suitable diameter, preferablybetween about 0.1 to 10 mm, more preferably about 0.1 to 1 mm, and mostpreferably about 0.15 to 0.5 mm. However, in other embodiments, thecapillary passage can have other non-uniform cross-sectionalconfigurations, which are defined by a maximum transverse dimension orwidth, or by a transverse cross-sectional area. For example, in apreferred embodiment, the capillary passage can have a transversecross-sectional area from about 8×10⁻⁵ mm² to about 80 mm², preferablyabout 2×10⁻³ mm² to about 8×10⁻¹ mm², and more preferably about 8×10⁻³mm² to about 2×10⁻¹ mm².

[0042] The flow passage 128 may be configured to extend in a linear ornon-linear direction. As shown in FIGS. 1 and 2, a portion of the flowpassage 128 is disposed within a body 129. In a preferred embodiment,the flow passage 128 comprises a section of tubing supported coaxiallywithin the body 129. The body 129 has an inner transverse dimension orwidth larger than the tubing forming the flow passage. In a preferredembodiment, a rear wall 134 of the body 129 forms a seal about the outersurface of the tube defining the flow passage 128 to form a dead airspace 135 between the tube defining the flow passage 128 and the body129. The body 129 is preferably air impermeable.

[0043] The body 129 can have various shapes, such as cylindrical, oval,polygonal, or conical. The body can be any suitable material, such as ametal, ceramic, polymer, glass, or a mixture or composite thereof. In apreferred embodiment, the body is made of a thermally insulatingmaterial to minimize loss of heat of air within the space 135 andthereby minimize heat loss from the tube defining the flow passage 128.By minimizing heat loss from the flow passage, it is possible to reducethe time needed to heat the flow passage to a desired temperature tovaporize liquid in the flow passage, and/or to heat the flow passage toa more uniform temperature. In a preferred embodiment, the flow passagecan be heated by passing electrical current through a heater comprisinga resistive heating material, such as a section of metal tubing formingthe flow passage, or a separate heater can be located along the flowpassage. For example, direct current can be passed through resistiveheating material via electrical lines 126 a, 126 b attached to positiveand negative electrodes of battery 126.

[0044] As shown in FIG. 2, an aerosol confinement sleeve 140 is providedabout the body 129 and flow passage 128. As described in detail below,the aerosol confinement sleeve 140 controls the aerosol particle size ofaerosols delivered by the aerosol generating device 120.

[0045] In the aerosol generating device 120 shown in FIG. 1, when thecontroller 124 activates the power supply to pass electrical currentthrough the heater formed by the resistive heating material, liquid inthe flow passage 128 is heated to a sufficient temperature to bevaporized. In a preferred embodiment, the aerosol generating device 120includes a power supply, which supplies electric current to the heaterformed by a portion of a metallic tube, such as a stainless steel tube,between electrical contacts (not shown) on the tube to which lines 126 aand 126 b are attached. However, in embodiments where the aerosolgenerating device is a larger laboratory or industrial unit, power canbe supplied by an external power source. As the power supply supplieselectric current, the electric current resistively heats the heatermaterial, thereby causing volatilization of liquid within the flowpassage 128. In a preferred embodiment, the controller 124 is programmedto activate the power supply in an intermittent manner so as to heat theflow passage 128 for a predetermined time interval during which apredetermined volume of fluid is supplied to the flow passage 128 fromthe source 122.

[0046] In other preferred embodiments, other arrangements can be used tovolatilize liquid within the flow passage 128. For example, a preferredembodiment comprises a laminate body including opposed layers bondedtogether, and a flow passage disposed between the layers, as describedin commonly-assigned U.S. application Ser. No. 09/742,320 filed Dec. 22,2000, the disclosure of which is hereby incorporated by reference in itsentirety.

[0047] In another preferred embodiment, an inductive heating arrangementcan be used, such as the arrangement disclosed in commonly-assigned U.S.application Ser. No. 09/742,323 filed on Dec. 22, 2000, the disclosureof which is hereby incorporated by reference in its entirety. In apreferred embodiment, a current is passed through one or more inductiveheating coils to produce an electromagnetic flux in an electricallyconductive heating element, which is located such that the flux produceseddy currents inside the heating element, which in turn heats theheating element. This heat is then transferred to the liquid within theflow passage 128 either by direct or indirect thermal conduction.

[0048] In another preferred embodiment, the heating arrangement includesa resistance heater, such as a thin platinum layer, located along theflow passage, as described in commonly-assigned U.S. Pat. Nos. 5,743,251and 6,234,167, each of which is hereby incorporated by reference in itsentirety.

[0049] In a preferred embodiment, the mouthpiece 132 has a volumetriccapacity of from about 5 cm³ to about 10 cm³. The mouthpiece 132includes a mouthpiece opening 132 a through which aerosol generated bythe aerosol generating device 120 exits to a patient inhaling theaerosol. In order to supply air for mixing with the volatilized liquidexiting from the flow passage 128, the aerosol generating device 120 caninclude one or more air passages 136 to permit the passage of externalair into the aerosol generating device 120. The external air passes intothe interior space 132 b defined by the mouthpiece 132. The external airinside the mouthpiece 132 admixes with the volatilized liquid exitingthe heated flow passage 128 within the mouthpiece 132. The mouthpieceopening 132 a is separated from the outlet end of the heated flowpassage 128 so that air passing into the space 132 b admixes with thevolatilized liquid prior to exiting through the mouthpiece opening 132a. Other gases (e.g., inert gases, nitrogen, or the like) suitable fordilution of medicament within the aerosol generating device may be mixedwith the volatilized fluid exiting the heated flow passage 128.

[0050] During operation of the aerosol generating device 120, the valve130 may be opened to allow a desired volume of liquid material from thesource 122 to enter the flow passage 128. The valve 130 may be openedeither prior to or subsequent to detection by the sensor 127 of vacuumpressure applied to the mouthpiece 132 by a user attempting to inhaleaerosol from the aerosol generating device 120. Liquid passing throughthe flow passage 128 is heated to a sufficient temperature to volatilizethe liquid. Liquid from the source 122 can be fed into the flow passage128 at a substantially constant pressure and/or in a predeterminedvolume. The volatilized liquid exits the flow passage 128 through anoutlet end of the flow passage 128 and forms an aerosol, which can beinhaled by a user drawing upon the mouthpiece 132.

[0051] The aerosol confinement sleeve 140 is provided in the aerosolgenerating device 120 to control the size distribution of aerosolparticles that are generated by the aerosol generating device 120. Asshown in FIG. 2, in a preferred embodiment, the aerosol confinementsleeve 140 is disposed at the outlet end of the flow passage 128 andbody 129 surrounding the flow passage. The aerosol confinement sleeve140 has a length, L, a largest cross-sectional dimension, W, and aninterior space 142 having an interior volume. In a preferred embodiment,the length L of the aerosol confinement sleeve 140 is from about ¼ inchto about 4 inches; dimension W is from about ¼ inch to about 2 inches;the ratio of the dimension W to the length L is from about 1:1 to about0.25:4; and the interior volume of the aerosol confinement sleeve 140 isfrom about 0.05 in³ to about 50 in³. In another preferred embodiment,the length L of the aerosol confinement sleeve 140 is from about ⅛ inchto about 2 inches, and dimension W is from about ⅛ inch to about ½ inch.

[0052] The shape of the aerosol confinement sleeve 140 is not limited.The aerosol confinement sleeve 140 can have any suitable shape, such ascylindrical, oval, polygonal, or conical. In a preferred embodiment, theaerosol confinement sleeve 140 is tubular and sized to fit closely ontothe body 129. The aerosol confinement sleeve 140 can be made of anysuitable material, such as a metal, ceramic, polymer, glass, or amixture thereof. In a preferred embodiment, the aerosol confinementsleeve is air impermeable.

[0053] The length L and dimension W of the aerosol confinement sleeve140 can be varied to control the size distribution of aerosol particlesdelivered by the aerosol generating device 120. As described below, ithas been determined that for a given flow rate of liquid in the flowpassage 128, increasing the length L of the aerosol confinement sleeve140 having a given dimension W can increase the mass median aerodynamicdiameter (MMAD) of aerosol particles delivered by the aerosol generatingdevice. Thus, by controlling the dimension W and length L of the aerosolconfinement sleeve 140, a selected aerosol size distribution or massmedian aerodynamic diameter of aerosol particles can be delivered to auser with the aerosol generating device 120.

[0054] For deep lung penetration, a preferred embodiment of the aerosolconfinement sleeve 140 can be configured to provide aerosol particleshaving a mass median aerodynamic diameter in a range between about 0.2microns to about 0.5 microns. If central lung deposition is desired, theaerosol confinement sleeve 140 can be configured to provide aerosolparticles having a mass median aerodynamic diameter in a range betweenabout 1 micron and about 2 microns. Furthermore, if deposition in theupper respiratory tract for medicaments, such as bronchodilators, isdesired, a larger particle size can be delivered by an appropriateconfiguration of the aerosol confinement sleeve 140.

[0055] In a preferred embodiment, the aerosol confinement sleeve 140 isremovably attached to the body 129 by any suitable connection (e.g., athreaded connection, snap-fit connection, or friction fit) so that oneaerosol confinement sleeve may be interchanged with a different aerosolconfinement sleeve having a different configuration in order to deliveraerosols having a different size distribution using the same capillarypassage 128 and heater. Therefore, the aerosol generating device 120 maybe adaptable for different targeted aerosol depositions for users. Suchinterchangeability of the aerosol confinement sleeve is also useful inlaboratory aerosol generating devices used to study aerosol formation,or in commercial devices in which a certain aerosol particle size may bedesired.

[0056] In a preferred embodiment, the body 129 can have approximatelythe same inner diameter as the aerosol confinement sleeve 140. Inanother preferred the body 129 can have a different (e.g., larger) innerdiameter than the aerosol confinement sleeve 140.

[0057] To further illustrate, if a user having the aerosol generatingdevice 120 configured for lung delivery of an aerosol desires to use theaerosol generating device 120 for upper respiratory tract delivery,which utilizes a larger aerosol particle size, the aerosol confinementsleeve 140 configured for lung penetration can be replaced with oneconfigured for upper respiratory tract aerosol delivery.

[0058] As shown in FIG. 1, the aerosol confinement sleeve 140 can extendinto the space 132 b of the mouthpiece 132. Depending on the length L ofthe aerosol confinement sleeve 140, the location of the outlet of theaerosol confinement sleeve in the space 132 b can be selectively varied.

[0059] As depicted in FIG. 2, volatilized material 143 exiting the flowpassage 128 enters the interior space 142 of the aerosol confinementsleeve 140. Air in the interior space 142 admixes with the volatilizedmaterial, which forms an aerosol, such as a condensation aerosol, whenthe vapor is cooled by the air. The aerosol exits from the outlet end ofthe aerosol confinement sleeve 140 and is inhaled by a user drawing onthe mouthpiece 132.

[0060] As described further below, it has been determined that for agiven dimension W of the aerosol confinement sleeve 140, increasing thelength L of the aerosol confinement sleeve 140 increases the size ofaerosol particles produced with the aerosol generating device. It hasfurther been determined that by decreasing the dimension W of theaerosol confinement sleeve, the length L of the aerosol confinementsleeve for producing a selected aerosol size is decreased. Accordingly,the length L and dimension W can be selectively varied to produceaerosols having selected particle sizes.

[0061] The source 122 may contain a suitable liquid aerosol formulation,such as a solution or suspension of a carrier and one or more othercomponents, depending on the intended application of the aerosol. Forexample, the carrier can be water and/or propylene glycol (PG). In apreferred embodiment, the liquid aerosol formulation includes a liquidcarrier and a liquid and/or particulate medicament. The medicament canbe any suitable medicament that can be delivered via an aerosol. Forexample, suitable medicaments include, but are not limited to,analgesics, anginal preparations, anti-allergics, antibiotics,antihistamines, antitussives, bronchodilators, diuretics,anticholinergics, hormones, and anti-flammatory agents, such as thosedescribed in U.S. Pat. No. 6,153,173, which is incorporated herein byreference in its entirety. The liquid aerosol formulation can beselected to provide a desired dose of the medicament via aerosolinhalation.

[0062] However, the liquid aerosol formulation does not have to includea medicament. For example, the liquid aerosol formulation may includesubstances, such as paints, scents, or fuels for research, commercial orindustrial applications.

EXAMPLES

[0063] The following examples demonstrate features of the invention. Theexamples are not intended to and should not be interpreted as limitingthe invention.

Example 1

[0064] Tests were conducted to demonstrate the effect of an aerosolconfinement sleeve on aerosol particle size and the percent recovery ofa liquid aerosol formulation. The arrangement tested included acylindrical, plastic body surrounding a flow passage heated by a 28gauge/44 mm CTP heater. The body had a ⅜ inch inner diameter and a ½inch outer diameter. Three cylindrical aerosol confinement sleeves eachhaving a ½ inch inner diameter, but having different lengths of 0.75inch, 1 inch and 1.5 inch, were separately fitted on the body. Anaerosol was produced using PG for the different arrangements. The bodywas constructed to prevent air flow into the upstream end of the spacebetween the body and the flow passage. For comparative purposes, in onetest an aerosol confinement sleeve was not used. The aerosols producedduring the four tests were collected in a cascade impactor (model MOUDIfrom MSP Corporation, Minneapolis, Minn.). As shown in FIG. 3, theaerosol confinement sleeves increased the MMAD of PG from about 0.75microns (for the comparative example having no aerosol confinementsleeve) to about 2.75 microns for the aerosol confinement sleeve lengthof 1.5 inch. The aerosol was analyzed to determine the percentagerecovery of PG. As shown in FIG. 4, the PG recovery decreased withincreasing aerosol confinement sleeve length. This result is attributedto increased deposition of PG on the inner surface of the aerosolconfinement sleeve. The test results show that an approximatelythree-fold increase in the MMAD can be achieved at a recovery of about65% when using the aerosol confinement sleeve.

Example 2

[0065] Tests were conducted to determine the effect of the inhalationflow rate of a user on the MMAD of aerosol particles generated frompropylene glycol (PG) supplied at a flow rate of 5 mg/sec with anaerosol generating device. Two cylindrical air intake passages supplyingair to the mouthpiece having respectively different inner diameters of ⅞inch and ¼ inch were used. Different users of an aerosol generatingdevice, such as the aerosol generating device 120, are expected toinhale on the mouthpiece at different air flow rates. The test resultsare shown in FIG. 5, in which Curve A represents the results for the airintake passage having a ⅞ inch inner diameter, and Curve B the resultsfor the air intake passage having a ¼ inch inner diameter. The resultsin Curves A and B demonstrate that the inhalation flow rate (air flowrate) of a user can significantly affect the MMAD of aerosol particlesat low air flow rates (i.e., less than about 15 Lpm), but that the MMADis relatively independent of the air flow rate over a range of valuesfrom about 15 Lpm to about 120 Lpm. Comparing Curves A and B, it can beseen that the MMAD of PG was higher at a given air flow rate for the airintake passage having the larger inner diameter. The air flow rate rangeof about 15 Lpm to about 120 Lpm is expected to be broader than thatemployed by users. The increase in the MMAD of PG at lower air flowrates is believed to be due to the decreased rate of cooling of thevapor emitted from the flow passage under these conditions. Thisphenomena can be employed to produce larger aerosol particledistributions suitable for targeted deposition in the upper respiratorytract.

Example 3

[0066] Tests were conducted to demonstrate the effect of the aerosolliquid flow rate in the capillary passage and the size of the capillarypassage on the size of aerosol particles produced. As shown in FIG. 6,three different capillary passages having inner diameters of 0.27 mm,0.22 mm and 0.15 mm, respectively, were used to produce aerosols from PGat PG flow rates from about 0.75 mg/sec to about 5.25 mg/sec in thecapillaries. The MMAD of aerosol particles was increased by increasingthe inner diameter of the capillary passage. The effect of the aerosolliquid flow rate is small at higher flow rates. Accordingly, these testresults demonstrate that the capillary size is a more important controlparameter with respect to aerosol particle size than the liquid flowrate in the capillary passage.

Example 4

[0067] An aerosol was produced using an aerosol generating device from aPG/5% oleyl alcohol (OA) solution. The size distribution of the aerosolparticles was determined using a cascade impactor. As shown in FIG. 7,the resulting aerosol included particles of PG and OA, which hadrespectively different particle size distributions from each other.

Example 5

[0068] Aerosols were produced using an aerosol generating device fromPG/OA solutions having different concentrations of OA. FIG. 8illustrates the relationship between the MMAD of aerosolized PG andaerosolized OA in the different aerosols. The size distribution of theaerosol particles of PG and OA was determined using a cascade impactor.The effect of the OA concentration on the MMAD of both PG and OA wasmore significant at lower OA concentrations than at higherconcentrations. These results show that aerosol particle size can beaffected by the solute concentration of the liquid used to produce theaerosol. In addition, the test results show that aerosol particleshaving an MMAD of 0.4-1.2 microns can be achieved.

Example 6

[0069] A test was conducted to generate an aerosol from a solution ofanother low volatility carrier and solute. A 1% solution of budesonidein PG was vaporized in an aerosol generating device and admixed withambient air. The measured size distributions of the aerosol particles ofbudesonide and PG are shown in FIG. 9.

Example 7

[0070] A test was conducted to generate an aerosol from a solution of PGand another solute. A 1% solution of PEG 400 (a polyethylene glycolhaving a molecular weight of 400 g/mole) in PG was vaporized in anaerosol generating device and admixed with ambient air. The measuredsize distributions of the aerosol particles of PEG 400 and PG are shownin FIG. 10.

Example 8

[0071] Tests were conducted to study the variation in the MMAD of PGaerosol particles versus the aerosol confinement sleeve length, whichranged from 0.5 inch to 1.5 inch. The confinement sleeve inner diameterwas 0.5 inch for each of the different sleeve lengths. A 28 gauge/44 mmlong controlled temperature profile (CTP) heater was used at a 5 mg/secPG flow rate. Capillaries having a controlled temperature profileconstruction are described in commonly-assigned U.S. application Ser.No. 09/957,026, filed on Sep. 21, 2001, which is incorporated herein byreference in its entirety. The aerosol generated was collected with amouthpiece having an inner diameter of 1.25 inch. The mouthpiece wasarranged downstream of, in flow communication with, the aerosolconfinement sleeve. The aerosol confinement sleeve and the mouthpiecewere concentrically arranged so that an annular space existed betweenthe outer surface of the aerosol confinement sleeve and the innersurface of the mouthpiece. Air was drawn into the annular space andmixed with aerosol exiting the aerosol confinement sleeve. Triplicatetests were performed for each confinement sleeve length. Percent PGrecovery was measured under approximate steady-state conditions using aMOUDI cascade impactor.

[0072]FIG. 11 shows the MMAD of PG aerosol particles (Curve A) andpercent PG recovery (Curve B) versus aerosol confinement sleeve length.As shown, there is about a two-, four-, and six-fold increase inparticle size (from a reference value of 0.7 μm without a sleeve) forthe sleeve lengths of 1 inch, 1.25 inch and 1.5 inch, respectively.Percent PG recoveries are about 73%, 66% and 19% for the confinementsleeve lengths of 1 inch, 1.25 inch and 1.5 inch, respectively.

Example 9

[0073] The effect of the mouthpiece inner diameter on aerosol particlesize was measured using a 22 mm (⅞ inch) inner diameter mouthpiecearranged co-axially with aerosol confinement sleeves having a length of0.5 inch, 0.75 inch, and 1 inch. The PG flow rate was 5 mg/sec. In FIG.12, Curve A shows the MMAD of PG aerosol particles, and Curve B showsthe percent PG recovery. A four-fold aerosol particle size growth wasobserved for a sleeve length of 1 inch with a recovery of about 62%.Comparing FIG. 11 (Example 8), a similar four-fold growth with arecovery of about 66% was also observed for a longer aerosol confinementsleeve length of 1.25 inch.

[0074] A possible explanation for the difference in the results shown inFIGS. 11 and 12 is depicted in FIG. 13. In FIG. 13, A and B representapproximated air streamlines for the mouthpiece 150 having an innerdiameter of 1.25 inch and the mouthpiece 152 having an inner diameter of⅞ inch, respectively, disposed coaxially with a flow passage/aerosolconfinement sleeve 160. Streamline B representing the smaller-innerdiameter mouthpiece is based on a higher air velocity between theaerosol confinement sleeve and the mouthpiece 152, which increases thelength of the core region between the streamlines A and B where mixingoccurs at a slower rate. Streamline A representing the larger mouthpieceindicates that mixing and dilution are expected to be significantlyfaster due to a smaller core region, resulting in a smaller particlesize. This is shown in FIG. 14, which combines Curve A of FIG. 11 andcurve A of FIG. 12. As shown in FIG. 14, at a given sleeve length, theMMAD of PG aerosol particles is smaller for the mouthpiece having a 1.25inch inner diameter than for the mouthpiece having a ⅞ inch innerdiameter.

Example 10

[0075] A mouthpiece having an inner diameter of ¾ inch, and an aerosolconfinement sleeve having a ½ inch inner diameter and a length of ¾ inchwere used. The results are shown in FIG. 15. As shown in Curve A, therewas no significant difference in the MMAD of PG aerosol particles overthe flow rate range of 15 Lpm to 90 Lpm. The values for percent PGrecovery shown in Curve B are based on the amount in the impactor andunder approximate steady state conditions.

Example 11

[0076] An aerosol generator was tested using an aerosol confinementsleeve with a ⅜ sleeve inner diameter at a higher PG flow rate of 10mg/sec. FIG. 16 shows plots of the MMAD of the PG aerosol particles(Curve A), and percent PG recovery (Curve B, filter capture method)versus the aerosol confinement sleeve length. Two replicate tests wereperformed for each data point. FIG. 16 shows that about a two- andthree-fold growth in the PG MMAD can be achieved with ¼ inch and ½ inchlong aerosol confinement sleeves, respectively. The percent PG recoverywas relatively constant at about 85% up to a sleeve length of ½ inch.

[0077]FIG. 17 shows results for the same test configuration, but at alower PG flow rate of 5 mg/sec. As shown in Curve A, PG aerosol particlegrowth is lower for the ¼ inch and ½ inch aerosol confinement sleevesthan at 10 mg/sec (see FIG. 16). However, the MMAD of PG aerosolparticles levels off at about 2.7 μm for the longer aerosol confinementsleeve lengths of 0.75 inch and 1 inch.

Example 12

[0078] Example 12 demonstrates the use of an aerosol confinement sleevehaving a smaller ¼ inch inner diameter as compared to an aerosolconfinement sleeve inner diameter of ⅜ inch used in Example 11. The ¼inch inner diameter sleeves snap on to the end of the body of theaerosol generator and have about the same inner diameter and outerdiameter as the body. The PG mass flow rate was 10 mg/sec and thecollection air flow rate was 30 Lpm.

[0079]FIG. 18 shows the MMAD of PG aerosol particles (Curve A) andpercent PG recovery (Curve B) by aerosol mass in the MOUDI cascadeimpactor. An MMAD of PG aerosol particles of about 2.5 μm can beachieved with an aerosol confinement sleeve length of ⅝ inch with a PGrecovery of about 70% in the impactor. This is more than a three-foldgrowth in aerosol particle size. Triplicate runs were performed for eachconfinement sleeve length.

Example 13

[0080] The effect on aerosol particle size of an aerosol confinementsleeve for a medicament (albuterol) dissolved in PG was tested with a 1%w/w albuterol in PG solution. FIG. 19 shows the aerosol particle sizedistributions for PG and albuterol aerosol particles generated using anaerosol confinement sleeve having a ½ inch length and ¼ inch innerdiameter (Curves C and D, respectively) and without an aerosolconfinement sleeve (Curves A and B, respectively) at a formulation flowrate at 10 mg/sec. Without the confinement sleeve, the MMAD of PGaerosol particles was 0.69 μm and the MMAD of albuterol aerosolparticles was 0.37 μm. Both components fit a uni-modal lognormaldistribution. With the confinement sleeve, the MMAD of PG aerosolparticles increased to 0.83 μm and maintained its log-normality (CurveC). In contrast, the albuterol aerosol particle size distribution becamebi-modal with an MMAD value of 0.66 μm (Curve D). The percentagerecovery values of 72%, 60%, 62%, and 48% shown in FIG. 19 are based onthe mass collected in a cascade impactor. These test results with atwo-component liquid system show that the aerosol confinement sleeve canenhance aerosol particle growth of both components.

Example 14

[0081] The effect on aerosol particle size for a medicament dissolved inPG was tested with a lower 0.5% w/w albuterol in PG solution, and at aflow rate of 5 mg/sec. FIG. 20 shows the PG (total) aerosol particlesize distribution without an aerosol confinement sleeve (Curve A), andwith confinement sleeves having a length of 1 inch (Curve B), 1.25 inch(Curve C), and 1.5 inch (Curve D).

[0082] Referring to FIG. 20, the MMAD of PG aerosol particles increasesfrom 0.55 μm without a confinement sleeve to 1.55 μm with a 1.5 inchlong sleeve. This represents about a three-fold growth in PG aerosolparticle size. Table 1 below shows that impactor recovery (gravimetric)of PG is 79% for the 1.5 inch long confinement sleeve.

[0083]FIG. 21 shows the size distributions for the albuterol aerosolparticles for the 0.5% w/w albuterol in PG solution. The MMAD ofalbuterol aerosol particles increases from 0.42 μm without a sleeve to1.48 μm with a 1.5 inch long sleeve. This represents a 3.5-fold growthin albuterol particle size. Impactor recovery of albuterol was 79%without a confinement sleeve, and about 50% with the 1.5 inch longconfinement sleeve. TABLE 1 TOTAL (PG) ALBUTEROL Sleeve Length MMADRecovery MMAD Recovery None 0.55 μm 101% 0.42 μm 79% 1.00 in 0.78 μm 74% 0.50 μm 50% 1.25 in 0.89 μm  88% 0.76 μm 57% 1.50 in 1.55 μm  79%1.48 μm 50%

Example 15

[0084] In the Examples described above, aerosol confinement sleeves wereevaluated for aerosol particle size control with PG as the carrier. InExample 15, the ability of the confinement sleeves having an innerdiameter of ½ inch to enhance aerosol particle growth with a differentcarrier liquid, triacetin (glyceryl triacetate), was evaluated. A 28gauge/44 mm long CTP heater was used at a triacetin flow rate of 5mg/sec. Duplicate runs were conducted for each confinement sleevelength. The gravimetric method was used to measure the mass of triacetinon each impactor stage. The confinement sleeves had a ½ inch innerdiameter and varying lengths.

[0085] As shown in FIG. 22, without an aerosol confinement sleeve, theMMAD of triacetin aerosol particles is about 1 μm (Curve A). With a ¾inch long aerosol confinement sleeve, the aerosol particle size almostdoubled with no significant change in impactor recovery. With a 1.25inch long aerosol confinement sleeve, there was a three-fold growth inthe MMAD of triacetin aerosol particles with a recovery greater than 95%(Curve B). For the longest aerosol confinement sleeve length tested (1.5inch), there was a four-fold growth in aerosol particle size, but therecovery dropped to about 60%. The overall trends in particle growth andrecovery of triacetin are similar to those observed for PG.

Example 16

[0086] A solution of 5% w/w OA in PG was used as another two-componentsystem. A 28 gauge/44 mm long CTP heater was used at a formulation flowrate of 5 mg/sec. FIG. 23 shows the MMAD of OA aerosol particle (CurveA) and percent recovery of OA (Curve B) in the impactor for OA versusthe aerosol confinement sleeve length. The confinement sleeves had a ½inch inner diameter and lengths of ¾ inch, 1 inch, 1.25 inch, and 1.5inch. Without a sleeve, the average MMAD of OA aerosol particles was0.39 μm with an impactor recovery of 78%. The MMAD of OA aerosolparticles approximately doubled at a confinement sleeve length of 1.25inch while maintaining a good impactor recovery of 83%. At the longestsleeve length of 1.5 inch, the MMAD of OA aerosol particles increased bya factor of about 3.5 as compared to using no confinement sleeve.Average impactor recovery for the longest confinement sleeve length was73%, as compared to 78% with no confinement sleeve.

[0087]FIG. 24 shows the MMAD of PG aerosol particles (Curve A) and PGrecoveries (Curve B) versus the aerosol confinement sleeve length. Forthe longest confinement sleeve length of 1.5 inch, the growth factor ofPG aerosol particles was about 2.7.

[0088]FIG. 25 shows the aerosol particle size distribution for OA forthe different sleeve lengths. The average MMAD of OA aerosol particlesincreases from 0.39 μm without a confinement sleeve to 1.38 μm with aconfinement sleeve length of 1.5 inch, which represents a growth factorof about 3.5. The size distribution for OA aerosol particles with noconfinement sleeve is bi-modal with a significant ultrafine or filterfraction. As the confinement sleeve length is increased, the sizedistribution moves towards uni-modality and a significantly reducedultrafine fraction. Moreover, at the longest sleeve length of 1.5 inch,the size distributions for OA and PG aerosol particles have asignificant overlap.

[0089] For the case of OA, total recoveries (impactor+elbow+sleeve)ranged between 85% and 93% for the different sleeve lengths. The maximumsleeve loss was about 9% for the longest sleeve length of 1.5″. Lossesin the elbow ranged from 3% to 7%.

Example 17

[0090] Example 17 used a 5% w/w OA in PG solution to test the effect ofthe airflow rate past the flow passage and confinement sleeve. Theconfinement sleeve length was 1.25 inch and the airflow rate past thesleeve was varied from 15 Lpm to 120 Lpm. The effect of inhalation rateon the MMAD of OA aerosol particles, which was used as a model drug, wasinvestigated. The flow rate of the 5% OA/PG formulation was set at 5mg/sec. A 22 mm (⅞ inch) inner diameter mouthpiece was used. The MMAD ofOA aerosol particles was about 1 μm, which is significantly higher thanthe 0.74 μm size obtained using a standard elbow (1.25 inch innerdiameter) in Example 16. A 28 gauge/44 mm long CTP heater was used.Triplicate runs were performed for each airflow rate condition.

[0091]FIG. 26 shows that at the standard MOUDI flow rate of 30 Lpm, theMMAD of OA aerosol particles is about 1.07 μm. Increasing the airflowrate to 90 and 120 Lpm, the MMAD of OA aerosol particles decreases byabout 26% and 39%, respectively.

[0092]FIG. 27 shows the MMAD of PG aerosol particles. Over the expectedrange of inhalation rates of the aerosol generator, 30 to 90 L/min, theparticle size is relatively consistent.

[0093] The test results demonstrate that the length of the aerosolconfinement sleeve can be selected to control aerosol particle size toenable the delivery of aerosols for different applications. For example,aerosols can be produced for delivering medicaments via inhalation forpulmonary delivery (utilizing small particle sizes) to upper respiratorytract delivery (utilizing larger particle sizes). Aerosols having aselected size distribution can be delivered over a broad range ofinhalation rates. In addition, aerosol generating devices including anaerosol confinement sleeve can be used to produce aerosols havingcontrolled aerosol size distributions for other applications, includingthe production of aerosols for forming coatings, such as paints,delivering scents, and depositing materials in microelectronicapplications.

[0094] The above are exemplary modes of carrying out the invention andare not intended to be limiting. It will be apparent to those ofordinary skill in the art that modifications thereto can be made withoutdeparture from the spirit and scope of the invention as set forth in theaccompanying claims.

What is claimed is:
 1. An aerosol generating device, comprising: ahousing having a flow passage therein; a heater arranged along the flowpassage and operable to vaporize liquid passing through the flowpassage; a source of a liquid to be volatilized in fluid communicationwith an inlet of the flow passage; and an aerosol confinement sleevelocated at the outlet end of the flow passage, the aerosol confinementsleeve having an interior configuration which controls a droplet sizedistribution of an aerosol delivered by the aerosol generating device.2. The aerosol generating device of claim 1, wherein the flow passageextends in a linear or non-linear direction and is a capillary sizedpassage.
 3. The aerosol generating device of claim 1, wherein the flowpassage is located in a monolithic or multilayer body of an electricallyinsulating material, and/or the flow passage has a uniform cross sectionalong the length thereof.
 4. The aerosol generating device of claim 1,which is a hand-held inhaler including a mouthpiece, the flow passage isa capillary sized passage, and the outlet of the flow passage directsvolatilized liquid into the aerosol confinement sleeve such that anaerosol is delivered to an interior of the mouthpiece.
 5. The aerosolgenerating device of claim 1, further comprising a mouthpiece whichincludes a mouthpiece opening through which aerosol is delivered to apatient, the outlet end of the flow passage being separated from themouthpiece opening by a predetermined distance.
 6. The aerosolgenerating device of claim 1, wherein the flow passage is located in acapillary tube, the device further comprising a body surrounding aportion of the capillary tube such that a space is defined between thecapillary tube and the body.
 7. The aerosol generating device of claim6, wherein the aerosol confinement sleeve is removably attached to thebody.
 8. The aerosol generating device of claim 6, wherein the body isof a thermally insulating material.
 9. The aerosol generating device ofclaim 1, wherein the aerosol confinement sleeve has a length of fromabout ¼ inch to about 4 inches.
 10. The aerosol generating device ofclaim 1, wherein the aerosol confinement sleeve has a largest transversedimension of from about ¼ inch to about 2 inches.
 11. The aerosolgenerating device of claim 1, wherein the aerosol confinement sleeve hasa ratio of a largest transverse dimension to a length thereof of fromabout 1:1 to about 0.25:4.
 12. The aerosol generating device of claim 1,wherein the aerosol confinement sleeve has a length of from about ¼ inchto about 4 inches, a largest transverse dimension of from about ¼ inchto about 2 inches, and a ratio of the largest transverse dimension tothe length thereof of from about 1:1 to about 0.25:4.
 13. The aerosolgenerating device of claim 1, wherein the aerosol confinement sleeve ispartially disposed in an interior of a mouthpiece of a hand-heldinhaler.
 14. The aerosol generating device of claim 1, wherein theliquid comprises a medicament.
 15. The aerosol generating device ofclaim 14, wherein the medicament is at least one substance selected fromthe group consisting of analgesics, anginal preparations,anti-allergics, antibiotics, antihistimines, antitussives,bronchodilators, diuretics, anticholinergics, hormones, andanti-flammatory agents.
 16. The aerosol generating device of claim 13,wherein the interior of the mouthpiece has a volumetric capacity in arange of from about 5 cc to about 10 cc.
 17. The aerosol generatingdevice of claim 1, further comprising a power supply arranged to supplyelectrical current to the heater, wherein the supplied electricalcurrent resistively heats the heater and volatilizes liquid in the flowpassage.
 18. The aerosol generating device of claim 17, furthercomprising a controller operably connected to the power supply toactivate the heater.
 19. A method for generating an aerosol, comprising:supplying liquid to a flow passage having an outlet end; heating theliquid so as to volatilize liquid in the flow passage; directing thevolatilized liquid out of the outlet end of the flow passage into anaerosol confinement sleeve located at the outlet end of the flowpassage; and admixing the volatilized liquid with air to produce anaerosol.
 20. The method of claim 19, wherein the liquid comprises amedicament.
 21. The method of claim 19, further comprising using anaerosol confinement sleeve having a length and/or a largest transversedimension to achieve a desired size of aerosol particles of the aerosol.22. The method of claim 19, wherein the flow passage is in a capillarytube, the method further comprising placing a body of a thermallyinsulating material in surrounding relationship to the capillary tube tocontrol heat loss from the capillary tube.
 23. The method of claim 19,wherein the aerosol confinement sleeve is removably attached to anoutlet end of the body.
 24. The method of claim 19, wherein the aerosolconfinement sleeve has a length of from about ¼ inch to about 4 inches.25. The method of claim 19, wherein the aerosol confinement sleeve has alargest transverse dimension of from about ¼ inch to about 2 inches. 26.The method of claim 19, wherein the aerosol confinement sleeve has aratio of a largest transverse dimension to a length thereof of fromabout 1:1 to about 0.25:4.
 27. The method of claim 19, wherein theaerosol confinement sleeve has a length of from about ¼ inch to about 4inches, a largest transverse dimension of from about ¼ inch to about 2inches, and a ratio of the largest transverse dimension to the lengththereof of from about 1:1 to about 0.25:4.
 28. The method of claim 20,wherein the medicament is at least one substance selected from the groupconsisting of analgesics, anginal preparations, anti-allergics,antibiotics, antihistamines, antitussives, bronchodilators, diuretics,anticholinergics, hormones, and anti-flammatory agents.
 29. The aerosolgenerating device of claim 1, wherein the aerosol confinement sleeve hasa length of from about ⅛ inch to about 2 inches.
 30. The aerosolgenerating device of claim 1, wherein the aerosol confinement sleeve hasa largest transverse dimension of from about ⅛ inch to about ½ inch. 31.The aerosol generating device of claim 1, further comprising a bodysurrounding a portion of the flow passage such that a space is definedbetween the capillary passage and the body, the aerosol confinementsleeve being attached to the body, the body having a first innerdiameter and the aerosol confinement sleeve having a second innerdiameter, wherein (i) the first inner diameter is approximately equal tothe second inner diameter, or (ii) the first inner diameter is smallerthan the second inner diameter.
 32. The method of claim 19, wherein theaerosol confinement sleeve has a length of from about ⅛ inch to about 2inches.
 33. The method of claim 19, wherein the aerosol confinementsleeve has a largest transverse dimension of from about ⅛ inch to about½ inch.
 34. The method of claim 19, wherein a body surrounds a portionof the flow passage such that a space is defined between the capillarypassage and the body, the aerosol confinement sleeve being attached tothe body, the body having a first inner diameter and the aerosolconfinement sleeve having a second inner diameter, wherein (i) the firstinner diameter is approximately equal to the second inner diameter, or(ii) the first inner diameter is smaller than the second inner diameter.35. An aerosol generating device, comprising: a flow passage; a heaterarranged along the flow passage and operable to vaporize liquid passingthrough the flow passage; and an aerosol confinement sleeve located atan outlet end of the flow passage, the aerosol confinement sleeve havingan interior configuration which controls a droplet size distribution ofan aerosol delivered by the aerosol generating device.
 36. The aerosolgenerating device of claim 35, wherein the flow passage is capillarysized.
 37. The aerosol generating device of claim 35, wherein theaerosol confinement sleeve has a length of from about ⅛ inch to about 2inches, and a largest transverse dimension of from about ⅛ inch to about½ inch.
 38. The aerosol generating device of claim 35, furthercomprising a body surrounding a portion of the flow passage such that aspace is defined between the flow passage and the body, the aerosolconfinement sleeve being attached to the body, the body having a firstinner diameter and the aerosol confinement sleeve having a second innerdiameter, wherein (i) the first inner diameter is approximately equal tothe second inner diameter, or (ii) the first inner diameter is smallerthan the second inner diameter.
 39. The aerosol generating device ofclaim 35, further comprising a mouthpiece which includes a mouthpieceopening through which aerosol is delivered to a patient.
 40. The aerosolgenerating device of claim 35, further comprising a source of a liquidto be volatilized in fluid communication with an inlet of the flowpassage.